Advertisement

Cholesterol Side Chain Cleavage Cytochrome P450 (P450scc)

  • L. E. Vickery
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 105)

Abstract

Cytochrome P450scc (CYPllA1) catalyzes the initial step in the biosynthesis of steroid hormones, the conversion of cholesterol to pregnenolone. This is the rate-determining step in the synthetic pathway and is a key site of regulation (Stone and Hector 1955; Koritz and Kramer 1970). Cytochrome P450scc is found at high levels in steroidogenic tissues, most notably the adrenal cortex, ovary, testes, and placenta, and is localized in the inner mitochondrial membrane (Churchill et al. 1978; Mitani et al. 1982). The enzymology, cellular regulation, and molecular biology of cytochrome P450scc have been extensively studied, and several comprehensive reviews can be found in chapters of a recent treatise on steroid biogenesis (cf. Usanov et al. 1990; Lambeth 1990; Waterman and Simpson 1990)

Keywords

Adrenal Cortex Cytochrome P450 Enzyme Steroidogenic Enzyme Sterol Carrier Protein Adrenal Steroidogenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abraham GE, Buster JE, Kyle FW, Corrales PC, Teller RC (1973) Radioimmunoassay of plasma pregnenolone. J Clin Endocrinol Metab 37: 40–45PubMedCrossRefGoogle Scholar
  2. Ahlgren R, Simpson ER, Waterman MR, Lundt J (1990) Characterization of the promoter/regulatory region of the bovine CYP11A (P-450scc) gene. J Biol Chem 265: 3313–3319PubMedGoogle Scholar
  3. Akhrem AA, Vasilevsky VI, Adamovich TB, Lapko AG, Shkumatov VM, Chashchin VL (1980) In: Biochemistry, biophysics, and regulation of cytochrome P-450. Elsevier, Amsterdam, pp 57–64Google Scholar
  4. Blum H, Leigh JS, Salerno JC, Ohnishi T (1978) The orientation of bovine adrenal cortex cytochrome P-450 in submitochondrial particle multilayers. Arch Biochem Biophys 187: 153–157PubMedCrossRefGoogle Scholar
  5. Burstein S, Middleditch BS (1974) Enzymatic formation of (20R 22R)-20,22- dihydroxycholesterol from cholesterol and a mixture of 16O2 and 18O2: random incorporation of oxygen atoms. Biochem Biophys Res Commun 61: 642–647CrossRefGoogle Scholar
  6. Burstein S, Middleditch BS, Gut M (1975) Mass spectrometric study of the enzymatic conversion of cholesterol to (22R)-22-hydryoxy cholesterol, (20R,22R)-20,22-dihydroxycholesterol, and pregnenolone, and of (22R)-22- hydroxycholestrerol to the glycol and pregnenolone in bovine adrenocortical preparations. J Biol Chem 250: 9028–9037PubMedGoogle Scholar
  7. Caron MG, Goldstein S, Savard K, Marsh JM (1975) Protein kinase stimulation of a reconstituted cholesterol side chain cleavage enzyme system in the bovine corpus luteum. J Biol Chem 250: 5137–5143PubMedGoogle Scholar
  8. Chung BC, Matteson KJ, Voutilainen R, Mohandas TK, Miller WL (1986) Human cholesterol side-chain cleavage enzyme, P450scc: cDNA cloning, assignment of the gene to chromosome 15, and expression in the placenta. Proc Natl Acad Sci USA 83: 8962–8966PubMedCrossRefGoogle Scholar
  9. Churchill PF, deAlvare LR, Kimura T (1978) Topological studies of the steroid hydroxylase complexes in bovine adrenocortical mitochondria. J Biol Chem 253: 4924–4929PubMedGoogle Scholar
  10. Coghlan VM, Vickery LE (1991) Site-specific mutations in human ferredoxin that affect binding to ferredoxin reductase and cytochrome P450scc. J Biol Chem 266: 18606–18612PubMedGoogle Scholar
  11. Coghlan VM, Vickery LE (1992) Electrostatic interactions stabilizing ferredoxin electron transfer complexes. Disruption by “conservative” mutations. J Biol Chem 267: 8932–8935PubMedGoogle Scholar
  12. Constantopoulos G, Tchen TT (1961) Cleavage of cholesterol side chain by adrenal cortex. J Biol Chem 236: 65–647PubMedGoogle Scholar
  13. Defaye G, Monnier N, Guidicelli C, Chambaz EM (1982) Phosphorylation of purified mitochondrial cytochromes P-450 (cholesterol desmolase and 11 beta-hydroxylase) from bovine adrenal cortex. Mol Cell Endocrinol 27: 157–168PubMedCrossRefGoogle Scholar
  14. DuBois RN, Simpson ER, Tuckey J, Lambeth JD, Waterman MR (1981) Evidence for a higher molecular weight precursor of cholesterol-side-chain-cleavage cytochrome P-450 and induction of mitochondrial and cytosolic proteins by corticotropin in adult bovine adrenal cells. Proc Natl Acad Sci USA 78: 1028–1032PubMedCrossRefGoogle Scholar
  15. Farese RV (1987) An update on the role of phospholipid metabolism in the action of steroidogenic agents. J Steroid Biochem 24: 737–743CrossRefGoogle Scholar
  16. Grahame-Smith DG, Butcher RW, Ney RL, Sutherland EW (1967) Adenosine 3′,5′-monophosphate as the intracellular mediator of the action of adrenocorticotropic hormone on the adrenal cortex. J Biol Chem 242: 5535–5541PubMedGoogle Scholar
  17. Groh SE, Nagahisa A, Tan SL, Orme-Johnson WH (1983) Electron spin echo modulation demonstrates P-450scc complexation. J Am Chem Soc 105: 7445–7446CrossRefGoogle Scholar
  18. Hall PF, Lewes JL, Lipson ED (1975) The role of mitochondrial cytochrome P-450 from bovine adrenal cortex in side chain cleavage of 20S,22R-dihydroxycholesterol. J Biol Chem 250: 2283–2286PubMedGoogle Scholar
  19. Hanukoglu I, Spitsberg V, Bumpus JA, Dus KM, Jefcoate CR (1981) Adrenal mitochondrial cytochrome p450scc. Cholesterol and adrenodoxin interactions at equilibrium and during turnover. J Biol Chem 256: 4321–4328PubMedGoogle Scholar
  20. Hashimoto T, Morohashi K, Omura T (1989) Cloning and characterization of bovine cytochrome P-450(11β) genes. J Biochem (Tokyo) 105: 676–679Google Scholar
  21. Hauffa BP, Miller WL, Grumbach MM, Conte FA, Kaplan SL (1985) Congenital adrenal hyperplasia due to deficient cholesterol side-chain cleavage activity (20,22-desmolase) in a patient treated for 18 years. Clin Endocrinol 23: 481–493CrossRefGoogle Scholar
  22. Heyl BL, Tyrrell DJ, Lambeth JD (1986) Cytochrome P450scc-substrate interactions. Role of the 3β- and side chain hydroxyls in binding to oxidized and reduced forms of the enzyme. J Biol Chem 261: 2743–2749PubMedGoogle Scholar
  23. Hume R, Kelly RW, Taylor PL, Boyd GS (1984) The catalytic cycle of cytochrome P-450scc and intermediates in the conversion of cholesterol to pregnenolone. Eur J Biochem 140: 583–591PubMedCrossRefGoogle Scholar
  24. Inoue H, Higashi Y, Morohashi K, Fujii-Kuriyama (1988) The 5′-flanking region of the human P-450(scc) gene shows responsiveness to cAMP-dependent regulation in a transient gene-expression system of Y-1 adrenal tumor cells. Eur J Biochem 171: 435–440Google Scholar
  25. Inoue H, Watanabe N, Higashi Y, Fujii-Kuriyama Y (1991) Structures of regulatory regions in the human cytochrome P-450scc (desmolase) gene. Eur J Biochem 195: 563–569PubMedCrossRefGoogle Scholar
  26. Iwahashi K, Ozaki HS, Tsubaki M, Ohnishi J, Takeuchi Y, Ichikawa Y (1990) Studies of the immunohistochemical and biochemical localization of the cytochrome P-450scc-linked monooxygenase system in the adult rat brain. Biochim Biophys Acta 1035: 182–189PubMedCrossRefGoogle Scholar
  27. Iwahashi K, Tsubaki M, Miyatake A, Miura S, Hosokawa K, Ichikawa Y (1991) Catalytic properties of cytochrome P-450scc from bovine and porcine adrenocortical mitochondria: effect of Tween20 concentration. J Steroid Biochem 38: 727–731CrossRefGoogle Scholar
  28. Iwamoto Y, Tsubaki M, Hiwatashi A, Ichikawa Y (1988) Crystallization of cytochrome P-450scc from bovine adrenocortical mitochondria. FEBS Lett 233: 31–36PubMedCrossRefGoogle Scholar
  29. Jacobs RE, Singh J, Vickery LE (1987) NMR studies of cytochrome P-450scc. Effects of steroid binding on water proton access to the active site of the ferric enzyme. Biochemistry 26: 4541–4545PubMedCrossRefGoogle Scholar
  30. Jefcoate CR, McNamara BC, DiBartolomeis (1986) Control of steroid synthesis in adrenal fasiculata cells. Endocr Res 12: 315–350Google Scholar
  31. John ME, Simpson ER, Carr BR, Magnus RR, Rosenfeld CR, Waterman MR, Mason JI (1987) Ontogeny of adrenal steroid hydroxylases: evidence for cAMP-independent gene expression. Mol Cell Endocrinol 50: 263–268PubMedCrossRefGoogle Scholar
  32. Katagiri M, Takikawa O, Sato H, Suhara K (1977) Formation of a cytochrome P-450scc-adrenodoxin complex. Biochem Biophys Res Commun 77: 804–809PubMedCrossRefGoogle Scholar
  33. Kimura T, Parcells JH, Wang HP (1978) Purification of adrenodoxin reductase, adrenodoxin, and cytochrome P-450 from adrenal cortex. Methods Enzymol 52: 132–142PubMedCrossRefGoogle Scholar
  34. Kirita S, Hahsimoto T, Kitajima M, Honda S, Morohashi K, Omura T (1990) Structural analysis of multiple bovine P-450(11β) genes and their promoter activities. J Biochem (Tokyo) 108: 1030–1041Google Scholar
  35. Koritz SB, Kumar AM (1970) On the mechanism of action of adrenocorticotropic hormone - the stimulation of the activity of enzymes involved in pregnenolone synthesis. J Biol Chem 245: 152–159PubMedGoogle Scholar
  36. Kuwada M, Kitajima R, Suzuki H, Horie S (1991) Purification and properties of cytochrome P-450 (SCC) from pig testis mitochondria. Biochem Biophys Res Commun 176: 1501–1508PubMedCrossRefGoogle Scholar
  37. Lambeth JD (1990) Enzymology of mitochondrial side-chain cleavage by cytochrome P450scc. In: Ruckpaul K, Rein H (eds) Molecular mechanisms of adrenal steroidogenesis and aspects of regulation and application. Taylor and Franceis, New York, p 58Google Scholar
  38. Lambeth JD, Kriengsiri S (1985) Cytochrome P-450scc-adrenodoxin interactions. Ionic effects on binding, and regulation of cytochrome reduction by bound steroid substrates. J Biol Chem 260: 8810–8816PubMedGoogle Scholar
  39. Lambeth JD, Stevens VL (1985) Cytochrome P-450scc: enzymology, and the regulation of intramitochondrial cholesterol delivery to the enzyme. Endocr Res 10: 283 - 309CrossRefGoogle Scholar
  40. Lambeth JD, Seybert DW, Kamin H (1980) Phospholipid vesicle-reconstituted cytochrome P-450SCC. Mutually facilitated binding of cholesterol and adrenodoxin. J Biol Chem 255: 138–143PubMedGoogle Scholar
  41. Lambeth JD, Kitchen SE, Farooqui AA, Tukey R, Kamin H (1982a) Cytochrome P450scc-substrate interactions. Studies of binding and catalytic activity using hydroxycholesterols. J Biol Chem 257: 1876–1884PubMedGoogle Scholar
  42. Lambeth JD, Seybert DW, Lancaster JR, Salerno JC, Kamin H (1982b) Steroidogenic electron transport in adrenal cortex mitochondria. Mol Cell Endocrinol 45: 13–31Google Scholar
  43. Lange R, Maurin L, Larroque C, Bienvenue A (1988) Interation of a spin-labelled cholesterol derivative with the cytochrome P-450scc active site. Eur J Biochem 172: 189–195PubMedCrossRefGoogle Scholar
  44. Larroque C, Van Lier JE (1980) The subzero temperature stabilized oxyferro complex of purified cytochrome P450scc. FEBS Lett 115: 175–177PubMedCrossRefGoogle Scholar
  45. Le Goascogne C, Robel P, Gouezou M, Sananes N, Baulieu E-E, Waterman M (1987) Neurosteroids: cytochrome P450scc in rat brain. Science 237: 1212–1215PubMedCrossRefGoogle Scholar
  46. Light DR, Orme-Johnson NR (1981) Beef adrenal cortical cytochrome P-450 which catalyzes the conversion of cholesterol to pregnenolone. Oxidation-reduction potentials of the free, steroid-complexed, and adrenodoxin-complexed P-450. J Biol Chem 256: 343–350PubMedGoogle Scholar
  47. Matocha MF, Waterman MR (1984) Discriminatory processing of the precursor forms of cytochrome P-450scc and adrenodoxin by adrenocortical and heart mitochondria. J Biol Chem 259: 8672–8678PubMedGoogle Scholar
  48. Matocha MF, Waterman MR (1985) Synthesis and processing of mitochondrial steroid hydroxylases. In vivo maturation of the precursor forms of cytochrome P-450scc, cytochrome P-450 lip, and adrenodoxin. J Biol Chem 260: 12259–12265Google Scholar
  49. Matteson KJ, Chung BC, Urdea MS, Miller WL (1986) Study of cholesterol side-chain cleavage (20,22 desmolase) deficiency causing congenital lipoid adrenal hyperplasia using bovine-sequence P450scc oligodeoxyribonucleotide probes. Endocrinology 118: 1296–1305PubMedCrossRefGoogle Scholar
  50. McMasters KM, Dickson LA, Shamy RV, Bobischon K, Macdonald GJ, Moyle WR (1987) Rat cholesterol side-chain cleavage enzyme (P-450scc): use of a cDNA probe to study the hormonal regulation of P-450scc mRNA levels in ovarian granulosa cells. Gene 57: 1–9PubMedCrossRefGoogle Scholar
  51. Minowa O, Sogawa K, Higashi Y, Fujii-Kuriyama Y (1990) Functional expression of microsomal and mitochondrial cytochrome P-450 (d and SCC) in COS-7 cells from cloned cDNA. Cell Struct Funct 15: 21–30PubMedCrossRefGoogle Scholar
  52. Mitani F, Shimizu T, Ueno R, Ishimura Y, Izumi S, Komatsu N, Watanabe K (1982) Cytochrome P-450 lip and P-450scc in adrenal cortex: zonal distribution and intramitochondrial localization by the horseradish peroxidase-labeled antibody method. J Histochem Cytochem 30: 1066–1074PubMedCrossRefGoogle Scholar
  53. Morisaki M, Duque C, Ikekawa N, Shikita M (1980) Substrate specificity of adrenocortical cytochrome P-450scc: I. Effect of structural modification of cholesterol side-chain on pregnenolone production. J Steroid Biochem 13: 545–550PubMedCrossRefGoogle Scholar
  54. Morisaki M, Duque C, Takane K, Ikekawa N, Shikita M (1982) Substrate specificity of adrenocortical cytochrome P-450scc: II. Effect of structural modification of cholesterol A/B ring to their side chain cleavage reaction. J Steroid Biochem 16: 101–105PubMedCrossRefGoogle Scholar
  55. Mornet E, Dupont J, Vitek A, White PC (1989) Characterization of two genes encoding human steroid 118-hydroxylase (P-450nP). J Biol Chem 264: 20961–20967PubMedGoogle Scholar
  56. Morohashi K, Fujii-Kuriyama Y, Okada Y, Sogawa K, Hirose T, Inayama S, Omura T (1984) Molecular cloning and nucleotide sequence of cDNA for mRNA.of mitochondrial cytochrome P-450(SCC) of bovine adrenal cortex. Proc Natl Acad Sci USA 81: 4647–4651PubMedCrossRefGoogle Scholar
  57. Morohashi K, Sogawa K, Omura T, Fujii-Kuriyama Y (1987) Gene structure of human cytochrome P-450(SCC), cholesterol desmolase. J Biochem (Tokyo) 101: 879–887Google Scholar
  58. Mulheron GW, Stone RT, Miller WL, Wise T (1989) Nucleotide sequence of cytochrome P-450 cholesterol side-chain cleavage cDNA isolated from procine testis. Nucllic Acids Res 17: 1773CrossRefGoogle Scholar
  59. Nagahisa A, Spencer RW, Orme-Johnson WH (1983) Acetylenic mechanism-based inhibitors of cholesterol side chain cleavage by cytochrome P-450scc. J Biol Chem 258: 6721–6723PubMedGoogle Scholar
  60. Nagahisa A, Spencer RW, Orme-Johnson WH (1984) Silicon-mediated suicide inhibition: an efficient mechanism-based inhibitor of cytochrome P-450scc oxidation of cholesterol. J Am Chem Soc 106: 166–1167CrossRefGoogle Scholar
  61. Ohta Y, Mitani F, Ishimura Y, Yanagibashi K, Kawamura M, Kawato S (1990) Conversion of cholesterol to pregnenolone mobilizes cytochrome P-450 in the inner membrane of adrenocortical mitochondria: protein rotation study. J Biochem (Tokyo) 107: 97–104Google Scholar
  62. Omura T, Sanders E, Estabrook RW, Cooper DY, Rosenthal O (1966) Isolation from adrenal cortex of a nonheme iron protein and a flavoprotein functional as a reduced triphosphopyridine nucleotide-cytochrome P-450 reductase. Arch Biochem Biophys 117: 660–673CrossRefGoogle Scholar
  63. Oonk RB, Parker KL, Gibson JL, Richards JS (1990) Rat cholesterol side-chain cleavage cytochrome P-450 (P-450scc) gene. Structure and regulation by cAMP in vitro. J Biol Chem 265: 22392–22401PubMedGoogle Scholar
  64. Orme-Johnson NR, Light DR, White-Stevens RW, Orme-Johnson WH (1979) Steroid binding properties of beef adrenal cortical cytochrome P450 which catalyzes the conversion of cholesterol to pregnenolone. J Biol Chem 254: 2103–2111PubMedGoogle Scholar
  65. Payne AH (1990) Hormonal regulation of cytochrome P450 enzymes, cholesterol side-chain cleavage and 17α-hydroxylase/C17-20 lyase in Lyase cells. Biol Reprod 42: 399–404PubMedCrossRefGoogle Scholar
  66. Pedersen RC, Browine AC (1983) Cholesterol side-chain cleavage in the rat adrenal cortex: isolation of a cycloheximide-sensitive activator peptide. Proc Natl Acad Sci USA 80: 1882–1886PubMedCrossRefGoogle Scholar
  67. Pedersen RC, Brownie AC (1987) Steroidogenesis-activator polypeptide isolated from a rat Leydig cell tumor. Science 236: 188–190PubMedCrossRefGoogle Scholar
  68. Pember SO, Powell GL, Lambeth JD (1983) Cytochrome P-450scc-phospholipid interactions. Evidence for a cardiolipin binding site and thermodynamics of enzyme interactions with cardiolipin, cholesterol, and adrenodoxin. J Biol Chem 258: 3198–3206PubMedGoogle Scholar
  69. Picado-Leonard J, Miller WL (1988) Homologous sequences in steroidogenic enzymes, steroid receptors and a steroid binding protein suggest a consensus steroid-binding sequence. Mol Endocrinol 2: 1145–1150PubMedCrossRefGoogle Scholar
  70. Privalle CT, McNamra BC, Dhariwal MS, Jefcoate CR (1987) ACTH control of cholesterol side-chain cleavage cytochrome P-450scc. Regulation of intramitochondrial cholesterol transfer. Mol Cell Endocrinol 53: 87–101PubMedCrossRefGoogle Scholar
  71. Rice DA, Kirkman MS, Aitken LD, Mouw AR, Schimmer BP, Parker KL (1990) Analysis of the promoter region of the gene encoding mouse cholesterol side-chain cleavage enzyme. J Biol Chem 265: 11713–11720PubMedGoogle Scholar
  72. Richards JS, Hedin L (1988) Molecular aspects of hormone action in ovarian follicular development, ovulation, and luteinization. Annu Rev Physiol 50: 441–463PubMedCrossRefGoogle Scholar
  73. Seybert DW, Lancaster JR Jr, Lambeth JD, Kamin H (1979) Participation of the membrane in the side chain cleavage of cholesterol. Reconstitution of cytochrome P-450scc into phospholipid vesicles. J Biol Chem 254: 12088–12098PubMedGoogle Scholar
  74. Shikita M, Hall PF (1973) Cytochrome P-450 from bovine adrenocortical mitochondria: an enzyme for the side chain cleavage of cholesterol: II. Subunit structure. J Biol Chem 248: 5605–5609PubMedGoogle Scholar
  75. Shikita M, Hall PF (1974) The stoichiometry of the conversion of cholesterol and hydroxycholesterols to pregnenolone catalyzed by adrenal cytochrome P-450. Proc Natl Acad Sci USA 71: 1441–1445PubMedCrossRefGoogle Scholar
  76. Shimizu T, Iizuka T, Mitani F, Ihsimura Y, Nozawa T, Hatano M (1981) Magnetic and natural circular dichroism spectra of cytochormes P-45011β and P-450scc purified from bovine adrenal cortex. Biochim Biophys Acta 669: 46–59PubMedGoogle Scholar
  77. Simpson DJ, Unkefer CJ, Whaley TW, Marrone BL (1991) A mechanism-based fluorogenic probe for the cytochrome P450 cholesterol side chain cleavage enzyme. J Org Chem 56: 5391–5396CrossRefGoogle Scholar
  78. Simpson ER, Boyd GS (1967) The cholesterol side chain cleavage system of bovine adrenal cortex. Eur J Biochem 2: 275–285PubMedCrossRefGoogle Scholar
  79. Simpson ER, Waterman MR (1988) Regulation of the synthesis of steroidogenic enzymes in adrenal cortical cells by ACTH. Annu Rev Physiol 50: 427–440PubMedCrossRefGoogle Scholar
  80. Sparkes RS, Klisak I, Miller WL (1991) Regional mapping of genes encoding human steroidogenic enzymes: P450scc to 15q23–q24, adrenodoxin to 11q22; adrenodoxin reductase to 17q24–q25; and P450cl7 to 10q24–q25. DNA Cell Biol 10: 359–365PubMedCrossRefGoogle Scholar
  81. Stone D, Hector O (1955) Studies on ACTH action in perfused bovine adrenals: aspects of progesterone as a intermediary in corticosteroidogenesis. Arch Biochem Biophys 54: 121–128PubMedCrossRefGoogle Scholar
  82. Suhara K, Gomi T, Sato H, Itagaki E, Takemore S, Katagiri M (1978) Purification and immunochemical characterization of two adrenal cortex mitochondrial cytochrome P-450 proteins. Arch Biochem Biophys 190: 290–299PubMedCrossRefGoogle Scholar
  83. Takemoto C, Nakano H, Sato H, Tamaoki B (1968) Fate of molecular oxygen required by endocrine enzymes for the side-chain cleavage of cholesterol. Biochim Biophys Acta 152: 749–757PubMedGoogle Scholar
  84. Takikawa O, Gomi T, Suhara K, Itagaki E, Takemori S, Katagiri M (1978) Properties of an adrenal cytochrome P-450 (P-450scc) for the side chain cleavage of cholesterol. Arch Biochem Biophys 190: 300–306PubMedCrossRefGoogle Scholar
  85. Tsubaki M, Hiwatashi A, Ichikawa Y (1986) Effects of cholesterol and adrenodoxin binding on the heme moiety of cytochrome P-450scc: a resonance Raman study. Biochemistry 25: 3563–3569PubMedCrossRefGoogle Scholar
  86. Tsubaki M, Iwamoto Y, Hiwatashi A, Ichikawa Y (1989) Inhibition of electron transfer from adrenodoxin to cytochrome P-450scc by chemical modification with pyridoxal 5′-phosphate: identification of adrenodoxin-binding site of cytochrome P450scc. Biochemistry 28: 6899–6907PubMedCrossRefGoogle Scholar
  87. Tuckey RC, Stevenson PM (1985) Purification and analysis of phospholipids in the inner mitochondrial membrane fraction of bovine corpus luteum, and properties of cytochrome P-450scc incorporated into vesicles prepared from these phospholipids. Eur J Biochem 148: 379–384PubMedCrossRefGoogle Scholar
  88. Tuls J, Geren L, Millett F (1989) Fluorescein isothiocyanate specifically modifies lysine 338 of cytochrome P-450scc and inhibits adrenodoxin binding. J Biol Chem 264: 16421–16425PubMedGoogle Scholar
  89. Usanov SA, Chashchin VL, Akhrem AA (1990) Cytochrome P450 dependent pathways of the biosynthesis of steroid hormones. In: Ruckpaul K, Rein H (eds) Molecular mechanisms of adrenal steroidogenesis and aspects of regulation and application. Taylor and Francis, New York, p 1Google Scholar
  90. Vahouny G, Chanderbhan R, Noland BJ, Scallen TJ (1984) Cholesterol ester hydrolase and sterol carrier proteins. Endocr Res 10: 473 - 505PubMedCrossRefGoogle Scholar
  91. Vickery LE (1991) Active site-directed inhibitors of steroid hydroxylase cytochromes P450. Methods Enzymol 206: 548–558PubMedCrossRefGoogle Scholar
  92. Vilgrain I, Defaye G, Chambaz EM (1984) Adrenocortical cytochrome P-450 responsible for cholesterol side chain cleavage (P-450scc) is phosphorylated by the calcium-activated, phospholipid-sensitive protein kinase (protein kinase C). Biochem Biophys Res Commun 125: 554–561PubMedCrossRefGoogle Scholar
  93. Wada A, Mathew PA, Barnes HJ, Sanders D, Estabrook RW, Waerman MR (1991) Expression of functional bovine cholesterol side chain cleavage P450 (P450scc) in Escherichia coli. Arch Biochem Biophys 290: 376–380PubMedCrossRefGoogle Scholar
  94. Walther B, Ghersi-Egea J-F, Minn A, Siest G (1987) Brain mitochondrial cytochrome P450scc: spectral and catalytic properties. Arch Biochem Biophys 254: 592–596PubMedCrossRefGoogle Scholar
  95. Waterman MR, Simpson ER (1990) Mechanisms of regulation of steroid hydroxylase gene expression. In: Ruckpaul K, Rein H (eds) Molecular mechanisms of adrenal steroidogenesis and aspects of regulation and application. Taylor and Francis, New York, p 101Google Scholar
  96. Xu T, Bowman EP, Glass DB, Lambeth JD (1991) Stimulation of adrenal mitochondrial cholesterol side-chain cleavage by GTP, steroidogenesis activator polypeptide (SAP), and sterol carrier protein2. GTP and SAP act synergistically. J Biol Chem 266: 6801–6807PubMedGoogle Scholar
  97. Xu X, Xu T, Robertson DG, Lambeth JD (1989) GTP stimulates pregnenolone generation in isolated rat adrenal mitochondria. J Biol Chem 264: 17674–17680PubMedGoogle Scholar
  98. Youngblood GL, Nesbitt MN, Payne AH (1989) The structural genes encoding P450scc and P450arom are closely linked on mouse chromosome 9. Endocrinology 125: 2784–2786PubMedCrossRefGoogle Scholar
  99. Zuber MX, Mason JI, Simpson ER, Waterman MR (1988) Simultaneous transfection of COS-1 cells with mitochondrial and microsomal steroid hydroxylases: incorporation of a steroidogenic pathway into nonsteroidogenic cells. Proc Natl Acad Sei USA 85: 699–703CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • L. E. Vickery

There are no affiliations available

Personalised recommendations